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New vaccine prototype provides unprecedented protection against brucellosis in mice

Dr. Zakia Goodwin and Dr. David Pascual analyze flow cytometry data relevant to their published study.

By Sarah Carey

A novel vaccine, developed by University of Florida researchers for use against a devastating strain of brucellosis that affects small ruminants, has shown groundbreaking effectiveness in conferring long-term immunity in mice.

David Pascual, Ph.D., a professor of infectious diseases at UF’s College of Veterinary Medicine, and his colleagues demonstrated the vaccine’s ability to generate a robust population of disease-fighting T cells in the lungs and spleen that helped to control systemic infection, they reported recently in Frontiers in Immunology.

“Although brucellosis is not a new disease and is believed to have existed since the domestication of livestock, the lack of effective vaccines has renewed efforts to develop more effective animal vaccines as well as human vaccines,” Pascual said, adding that live, attenuated brucellosis vaccines are used for livestock, but not for humans.

Now classified by the U.S. Centers for Disease Control and Prevention as a re-emerging pathogen, brucellosis continues to impact developing countries and persists in expanding populations of wildlife species in the United States, constantly threatening domestic herds with infection.

In the U.S., brucellosis persists in bison herds in Yellowstone, which can infect domestic livestock upon contact, resulting in lost pregnancy in infected cows. Elsewhere in the country, the disease is typically introduced into bovine herds by exploding populations of feral pigs. Worldwide, Brucella melitensis strain infects small ruminants with increased prevalence in recent years, due to multiple factors, including expansion of wildlife species. Humans are at risk of infection from consuming unpasteurized goat milk and cheeses, and infection can lead to rising and falling fevers, sweats, malaise and weakness, among other symptoms if left untreated.

Dr. Zakia Goodwin prepares a lymphocyte sample from this brucellosis study for flow cytometry analysis.

The new live, attenuated mucosal vaccine was tested using an oral delivery method followed by an intranasal boost — an approach few studies have investigated. Vaccines currently used against this strain of brucellosis are injected under the skin. This method does not target the disease’s primary infection route, which is through the mouth and nose, the researchers said.

“Other vaccines currently used to protect against Brucella melitensis are not ideal,” said Zakia Goodwin, D.V.M., Ph.D., a study co-author. “If your goal is disease eradication from a population, surveillance through testing is important to identify diseased animals. With some existing vaccines, it is difficult to distinguish naturally infected from vaccinated animals. This vaccine addresses this challenge and also provides equal or better protection as the others.”

The study was part of Goodwin’s doctoral research program at UF.

“A few years ago, brucellosis was considered a neglected tropical disease,” Goodwin said. “Now we’re seeing more and more cases in humans as well as in animals, causing it to be reclassified as a re-emerging pathogen.”

An increase in animal cases corresponds to an increase in human cases, she said.

“Our goal is to develop a better vaccine for animals and to ultimately develop a vaccine for humans as well,” Goodwin said, adding that the current study provided preliminary data on which to advance the team’s research.

“We have the vaccine; we’ve found that it works in a research animal model,” she said. “The next step would be to test it in a natural host, and to look more closely at exactly how long the protective response is. We’re already seeing that these T cells persist and are long-lived. This new vaccine is promising, because in comparison with the existing vaccines, the results are so stunning.”